complex biological system
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2021 ◽  
Vol 22 (S14) ◽  
Author(s):  
Paola Stolfi ◽  
Filippo Castiglione

Abstract Background The aim of the present paper is to construct an emulator of a complex biological system simulator using a machine learning approach. More specifically, the simulator is a patient-specific model that integrates metabolic, nutritional, and lifestyle data to predict the metabolic and inflammatory processes underlying the development of type-2 diabetes in absence of familiarity. Given the very high incidence of type-2 diabetes, the implementation of this predictive model on mobile devices could provide a useful instrument to assess the risk of the disease for aware individuals. The high computational cost of the developed model, being a mixture of agent-based and ordinary differential equations and providing a dynamic multivariate output, makes the simulator executable only on powerful workstations but not on mobile devices. Hence the need to implement an emulator with a reduced computational cost that can be executed on mobile devices to provide real-time self-monitoring. Results Similarly to our previous work, we propose an emulator based on a machine learning algorithm but here we consider a different approach which turn out to have better performances, indeed in terms of root mean square error we have an improvement of two order magnitude. We tested the proposed emulator on samples containing different number of simulated trajectories, and it turned out that the fitted trajectories are able to predict with high accuracy the entire dynamics of the simulator output variables. We apply the emulator to control the level of inflammation while leveraging on the nutritional input. Conclusion The proposed emulator can be implemented and executed on mobile health devices to perform quick-and-easy self-monitoring assessments.


Author(s):  
Jaimit Parikh ◽  
Timothy Rumbell ◽  
Xenia Butova ◽  
Tatiana Myachina ◽  
Jorge Corral Acero ◽  
...  

AbstractBiophysical models are increasingly used to gain mechanistic insights by fitting and reproducing experimental and clinical data. The inherent variability in the recorded datasets, however, presents a key challenge. In this study, we present a novel approach, which integrates mechanistic modeling and machine learning to analyze in vitro cardiac mechanics data and solve the inverse problem of model parameter inference. We designed a novel generative adversarial network (GAN) and employed it to construct virtual populations of cardiac ventricular myocyte models in order to study the action of Omecamtiv Mecarbil (OM), a positive cardiac inotrope. Populations of models were calibrated from mechanically unloaded myocyte shortening recordings obtained in experiments on rat myocytes in the presence and absence of OM. The GAN was able to infer model parameters while incorporating prior information about which model parameters OM targets. The generated populations of models reproduced variations in myocyte contraction recorded during in vitro experiments and provided improved understanding of OM’s mechanism of action. Inverse mapping of the experimental data using our approach suggests a novel action of OM, whereby it modifies interactions between myosin and tropomyosin proteins. To validate our approach, the inferred model parameters were used to replicate other in vitro experimental protocols, such as skinned preparations demonstrating an increase in calcium sensitivity and a decrease in the Hill coefficient of the force–calcium (F–Ca) curve under OM action. Our approach thereby facilitated the identification of the mechanistic underpinnings of experimental observations and the exploration of different hypotheses regarding variability in this complex biological system.


2021 ◽  
Author(s):  
Chiranjit Maji ◽  
Pratyay Sengupta ◽  
Anandi Batabyal ◽  
Hirok Chaudhuri

Abstract The stochastic nature of the human heart, a complex biological system, is evident from electrocardiogram (ECG) signals, which are weak, non-linear and non-stationary signals. These temporal variations of electromagnetic pulses emanated from the heart are instrumental in indicating the cardiac health. The Empirical Mode Decomposition (EMD) technique was employed in order to decompose a total of 64 ECG signal data of arrhythmic and normal subjects, obtained from widely used MIT-BIH databases, into a finite number of Intrinsic Mode Functions (IMFs). The rationale behind using this strategy was to extract non-linear features of ECG signals which are not explicitly expressed, while keeping the original signal unaltered. Following removal of non-stationary noises from the ECG signals by the Savitzky-Golay (SG) filter, popular non-linear parameter Hurst Exponent (H) was estimated for every IMF by employing the R/S technique. A distinct difference between H values of 1st IMFs between normal individuals and arrhythmia affected patients was identified. This observation was further validated through an age-based and gender-based analysis, which demonstrated a unique alteration pattern with age. The study showed 94.92% probability in detection of arrhythmia in a patient. Adopting this EMD-based procedure for ECG data analysis and disease prediction may assist in reducing our dependence on intuition-based diagnosis of ECG reports by medical practitioners and may provide novel insights into the functioning of the human heart which might help develop new biomedical strategies to combat cardiac disorders.


Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 973
Author(s):  
Preetha Rajendiran ◽  
Faizul Jaafar ◽  
Sonika Kar ◽  
Chenichery Sudhakumari ◽  
Balasubramanian Senthilkumaran ◽  
...  

The fish reproductive system is a complex biological system. Nonetheless, reproductive organ development is conserved, which starts with sex determination and then sex differentiation. The sex of a teleost is determined and differentiated from bipotential primordium by genetics, environmental factors, or both. These two processes are species-specific. There are several prominent genes and environmental factors involved during sex determination and differentiation. At the cellular level, most of the sex-determining genes suppress the female pathway. For environmental factors, there are temperature, density, hypoxia, pH, and social interaction. Once the sexual fate is determined, sex differentiation takes over the gonadal developmental process. Environmental factors involve activation and suppression of various male and female pathways depending on the sexual fate. Alongside these factors, the role of the brain during sex determination and differentiation remains elusive. Nonetheless, GnRH III knockout has promoted a male sex-biased population, which shows brain involvement during sex determination. During sex differentiation, LH and FSH might not affect the gonadal differentiation, but are required for regulating sex differentiation. This review discusses the role of prominent genes, environmental factors, and the brain in sex determination and differentiation across a few teleost species.


Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1119
Author(s):  
Kenneth K L Kwan ◽  
Tin Yan Wong ◽  
Anna X. D. Yu ◽  
Tina T. X. Dong ◽  
Henry H. L. Lam ◽  
...  

The therapeutic efficacy of a herbal mixture, being multi-target, multi-function and multi-pathway, is the niche of traditional Chinese medicine (TCM). Systems biology can dissect the network of signaling mechanisms in a complex biological system. In preparing TCM decoctions, the boiling of herbs together in water is a common practice; however, the rationale of this specific preparation has not been fully revealed. An approach of mass-spectrometry-based multi-omics was employed to examine the profiles of the cellular pathways, so as to understand the pharmacological efficacy of Danggui Buxue Tang (DBT), a Chinese herbal mixture containing Astragali Radix and Angelicae Sinensis Radix, in cultured rat osteoblasts and mesenchymal stem cells. The results, generated from omics analyses, were compared from DBT-treated osteoblasts to those of treating the herbal extract by simple mixing of extracts from Astragali Radix and Angelicae Sinensis Radix, i.e., herbal mixture without boiling together. The signaling pathways responsible for energy metabolism and amino acid metabolism showed distinct activation, as triggered by DBT, in contrast to simple mixing of two herbal extracts. The result supports that boiling the herbs together is designed to maximize the osteoblastic function of DBT, such as in energy and lipid metabolism. This harmony of TCM formulation, by having interactive functions of two herbs during preparation, is being illustrated. The systems biology approach provides new and essential insights into the synergy of herbal preparation. Well-defined multiple targets and multiple pathways in different levels of omics are the key to modernizing TCM.


2021 ◽  
Vol 9 ◽  
Author(s):  
Rodrigo Solis-Sosa ◽  
Arne Ø. Mooers ◽  
Maxim Larrivée ◽  
Sean Cox ◽  
Christina A. D. Semeniuk

The Monarch butterfly eastern population (Danaus plexippus) is in decline primarily due to habitat loss. Current habitat restoration programs focus on re-establishing milkweed, the primary food resource for Monarch caterpillars, in the central United States of America. However, individual components of the Monarch life cycle function as part of an integrated whole. Here we develop the MOBU-SDyM, a migration-wide systems dynamics model of the Monarch butterfly migratory cycle to explore alternative management strategies’ impacts. Our model offers several advances over previous efforts, considering complex variables such as dynamic temperature-dependent developmental times, dynamic habitat availability, and weather-related mortality across the entire range. We first explored whether the predominant focus of milkweed restoration in the mid-range of the Monarch’s migration could be overestimating the Monarch’s actual habitat requirements. Second, we examined the robustness of using the recommended 1.2–1.6 billion milkweed stems as a policy objective when accounting for factors such as droughts, changes in temperature, and the stems’ effective usability by the Monarchs. Third, we used the model to estimate the number and distribution of stems across the northern, central, and southern regions of the breeding range needed to reach a self-sustainable long-term Monarch population of six overwintering hectares. Our analysis revealed that concentrating milkweed growth in the central region increases the size of the overwintering colonies more so than equivalent growth in the south region, with growth in the northern region having a negligible effect. However, even though simulating an increase in milkweed stems in the south did not play a key role in increasing the size of the overwintering colonies, it plays a paramount role in keeping the population above a critically small size. Abiotic factors considerably influenced the actual number of stems needed, but, in general, our estimates of required stems were 43–91% larger than the number of stems currently set as a restoration target: our optimal allocation efforts were 7.35, 92, and 0.15% to the south, central, and northern regions, respectively. Systems dynamics’ analytical and computational strengths provided us with new avenues to investigate the Monarch’s migration as a complex biological system and to contribute to more robust restoration policies for this unique species.


Author(s):  
Oksana Chychenova

The paper considers the problem of today is a bad attitude to physical education in higher education. The health of every citizen is the main slogan of the country's policy. The human body is the only complex biological system that constantly interacts with environmental conditions. Health is a state of physical, moral, psycho- emotional, social, intellectual and harmonious development. Health is a reserve of organ capacity that needs to be improved during regular exercise training and a healthy lifestyle. Physical culture and sports are part of the general culture. As a safeguard, it helps to get rid of the negative aspects of life that hinder the development of the individual in a harmonious relationship with society. The level of physical activity of the country's population, by age, is below the minimum allowable. Hypodynamia is one of the leading causes of death and disability. The strategy for the development of physical culture, recommendation for the development of physical education and sports among students are state documents. They are developed with the participation of the specialists and sent for implementation to institutions. The help to direct forces to a new positive, responsible attitude ti physical training, physical working capacity of our future experts, heads, citizens of the country. The statistics provided in the documents finally prove that the crisis has reached significant proportions and may lead to negative consequences for Ukrainians and their future. Many factors and conditions can change the attitude of young people to physical culture and sports to a positive vision. The main thing is for young people to know that all the measures aimed at them have been implemented.


Author(s):  
Rupasree Brahma ◽  
H. Raghuraman

Protein hydration dynamics plays an important role in many physiological processes since protein fluctuations, slow solvation, and the dynamics of hydrating water are all intrinsically related. Red edge excitation shift (REES) is a unique and powerful wavelength-selective (i.e. excitation-energy dependent) fluorescence approach that can be used to directly monitor the environment-induced restriction and dynamics around a polar fluorophore in a complex biological system. This review is mainly focused on recent applications of REES and a novel analysis of REES data to monitor the structural dynamics, functionally relevant conformational transitions and to unmask the structural ensembles in proteins. In addition, the novel utility of REES in imaging protein aggregates in a cellular context is discussed. We believe that the enormous potential of REES approach showcased in this review will engage more researchers, particularly from life sciences.


Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. R79-R94 ◽  
Author(s):  
Leyla Sati

The circadian system regulates the daily temporal organization in behavior and physiology, including neuroendocrine rhythms and reproduction. Modern life, however, increasingly impacts this complex biological system. Due to limitations of working with human subjects exposed to shift work schedules, most chronoregulation research has used rodent models. Recent publications in these model systems have emphasized the negative effects of circadian rhythm disruption on both female and male reproductive systems and fertility. Additionally, there is growing concern about the long-term effects of circadian rhythm disruptions during pregnancy on human offspring and their descendants as circadian regulation during pregnancy can also alter epigenetic programing in offspring. However, to truly know if such concerns apply to humans will require retrospective and prospective human studies. Therefore, this review will highlight the latest available evidence regarding potential effects of chronodisruption on both female and male reproductive systems. Additionally, it presents a comprehensive summary of transgenerational and epigenetic effects on adult offspring that result from maternal chronodisruption.


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